Lyme disease is a multi-systemic infection caused by the pathogen Borrelia burgdorjeri. The black-legged tick, Ixodes scapularis, is the common vector for B. burgdorferi. This tick also transmits the agents of human granulocytic ehrlichiosis and babesiosis. The purpose of this project is to develop an anti-I. scapiilaris vaccine to block tick attachment and tick-mediated disease transmission. Rabbits or guinea pigs infested with I. scapularis acquire antibody-mediated resistance to tick bites, a phenomenon known as "tick-immunity.'' Phase I experiments evaluated Salp13 and Salp25D, two recombinant proteins expressed from I. scapularis salivary gland cDNAs, as candidate vaccines. Guinea pigs immunized with a combination of the two recombinant proteins demonstrated host resistance to tick bites. Phase II specific aims are to: (a) produce prototype Salp 13 and Salp25D vaccines suitable for extensive testing in animal models; (b) investigate Salp 13 and Salp25D contributions to the tick bite-induced tick immunity; and (c) determine if immunization with an optimized Salp13/Salp25D vaccine blocks pathogen transmission from ticks. These experiments will lead to Phase III development of a new vaccine designed to protect against multiple tick-borne pathogens. PROPOSED COMMERCIAL APPLICATION: A vaccine against Ixodes scapiilaris tick bites would potentially protect against several pathogens, including B. burgdorferi, Babesia microti, and the agent of human granulocytic ehrlichiosis. The commercial market would overlap with the market for LYMErix, a Glaxo SmithKline human Lyme disease vaccine, and the currently approved canine Lyme disease vaccines.